POS1059 EFFICACY OF UST IN ACTIVE PsA IS INDEPENDENT FROM CONCOMITANT MTX USE, EVEN IN PATIENTS WITH MORE SEVERE SKIN PSORIASIS: SUBGROUP ANALYSIS FROM A RANDOMIZED PLACEBO-CONTROLLED INVESTIGATOR INITIATED CLINICAL TRIAL
Authors: M. Köhm, T. Rossmanith, A. C. Foldenauer, H. Kellner, U. Kiltz, J. Rech, G. R. Burmester, D. M. Kofler, J. Brandt-Juergens, C. Jonetzko, H. Burkhardt, F. Behrens
Journal: Annals of the Rheumatic Diseases (2022)

Background The use of bDMARDs treatments in patients with psoriatic arthritis (PsA) usually requires treatment failure or intolerance of csDMARD/MTX before initiation. The value of MTX in combination with bDMARDs is still unclear. We designed an investigator-initiated, randomized, placebo-controlled trial (IIT) in active PsA to examine if outcomes of treatment with ustekinumab (UST) in combination with MTX (either newly initiated or ongoing) were different from UST only (+Placebo; PBO). With known efficacy of MTX on skin psoriasis outcomes may differ in patients with or without significant skin involvement of their psoriatic disease. Objectives To compare efficacy outcomes in UST+PBO vs UST+MTX in dependency of skin involvement (Body Surface Area [BSA]) at baseline. Methods A total of 186 patients with active PsA (defined as TJC≥4, SJC≥4 [68/66 joint count] and DAS28≥3.2) were screened for eligibility. 173 patients were randomized to UST+MTX (new or ongoing) or UST+PBO. With this post hoc subgroup analysis outcome parameters were compared between patients with or without skin psoriasis &gt; 3 % BSA. Demographic data and disease activity status of arthritis (joint count [TJC/SJC], DAPSA, DAS28), skin (PASI, BSA), HR-QoL (EQ5D, DLQI) and physical function (HAQ) were compared between groups. Results BL data were well-balanced between main treatment groups (UST+MTX, n=86; UST+PBO, n=74) including gender (42.5% vs 40.5% female) and mean values for age (49.2 vs 47.2 years), BMI (29.4 vs 28.9 kg/m2), SJC (8 vs 8), TJC (12 vs 12), DAS28-CRP (4.6 vs 4.4), DAPSA (36.7 vs 34.9) and PASI (2.8 vs 2.4. Disease activity remained well-balanced even after dividing groups according to skin involvement ((a) BSA ≤3% and (b) BSA &gt;3%) with a trend of more severe joint involvement (SJC, TJC) in BSA &gt;3% for UST+MTX compared to UST+PBO. At week 24, relative changes in TJC (-62% vs -62%), change in DAS28 and DAPSA were equal in all treatment groups independent from skin involvement (Table 1). Differences between the groups according to skin involvement were seen for relative changes in SJC (BSA &gt;3%: -74.8% UST+MTX vs -84.3% UST+PBO), subject global assessment (SGA), physician global assessment (PGA), DLQI and EQ5D. Highest levels for changes were detected in the UST+PBO group with high skin involvement (BSA &gt;3%). Table 1. Outcomes at Week 24 (LOCF ) UST+MTX UST+PBO BSA ≤3% BSA &gt;3% BSA ≤3% BSA &gt;3% n=46 n=40 n=51 n=23 TJC68 change from BL -7.83 (SD 10.3) -9.5 (SD 10.3) -8.9 (SD 9.5) -7.3 (SD 7.4) SJC66 change from BL -6.0 (SD 5.4) -7.1 (SD 3.5) -6.5 (SD 6.2) -6.4 (SD 3.8) PASI change from BL + -1.3 (SD 1.9) -8.5 (SD 9.6) -1.5 (SD 2.4) -9.0 (SD 10.7) DAS-28 ESR [mm/hr] change from BL -1.6 (SD 1.1) -1.8 (SD 1.2) -1.7 (SD 1.4) -1.8 (SD 1.1) DAS-28 CRP [mg/l] change to BL -1.5 (SD 1.2) -1.5 (SD 1.3) -1.6 (SD 1.2) - 1.7 (SD 1.1) DAPSA change from BL -17.4 (SD 16.8) -20.8 (SD 13.2) -20.5 (SD 16.6) -20.4 (SD 15.3) HAQ change from BL -0.1 (SD 0.4) -0.2 (SD 0.5) -0.3 (SD 0.3) -0.3 (SD 0.5) DLQI change from BL -3.1 (SD 5.5) -5.5 (SD 8.2) -2.3 (SD 3.3) -6.4 (SD 7.9) EQ5D VAS Health State change from BL 6.7 (SD 24.7) 11.7 (SD 23.6) 8.0 (SD 24.2) 21.3 (SD 25.3) Conclusion IL12/23 inhibition with UST is an effective treatment for active PsA independent of MTX use. Data from this IIT indicate that additional MTX has no positive impact on UST efficacy for arthritis, skin, HR-QoL and physical function. This independency of UST effect from MTX can also be demonstrated in patients with active skin involvement despite known efficacy of MTX for skin psoriasis. Acknowledgements We thank Janssen for support of the study with a research grant. Disclosure of Interests Michaela Köhm Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen, Tanja Rossmanith Grant/research support from: Janssen, Ann Christina Foldenauer Grant/research support from: Janssen, Herbert Kellner Speakers bureau: Janssen, Consultant of: Janssen, Uta Kiltz Speakers bureau: Abbvie, Fresenius, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Amgen, Biocad, Biogen, Chugai, Eli Lilly, Hexal, Grünenthal, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Amgen, Biogen, Fresenius, GSK, Hexal, Novartis, Pfizer, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Biogen, BMS, Chugai, GSK, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Gerd Rüdiger Burmester Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen, David M Kofler Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen, Jan Brandt-Juergens Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen, Christin Jonetzko Grant/research support from: Janssen, Harald Burkhardt Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen, Frank Behrens Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen